The Estrogen Elixir: A History of Hormone Replacement Therapy in America

2. From the ‘‘Neutral Gender’’ to ‘‘Feminine Forever’’

c h a p t e r t w o From the ‘‘Neutral Gender’’ to ‘‘Feminine Forever’’ Twenty-five years after Doisy and Allen arrived in St. Louis, another young man landed in the city to begin his scientific career. A recent medical graduate from the University of Rochester, this 28-year-old doctor moved to Missouri for an internship and residency in obstetrics and gynecology at St. Louis Maternity Hospital and Barnes Hospital of the Washington University School of Medicine. In 1947 he joined the faculty of the School of Medicine, rising from instructor to associate professor in the department of obstetrics and gynecology.∞ In the 1950s, he emerged as one of the architects of the campaign to expand the use of sex hormones from a short-term remedy to alleviate the symptoms of menopause to a long-term therapy to improve the health of older women; his ideas would have a lasting impact on the medical prescription of estrogen for the rest of the twentieth century. However, this influential body of research, reported in more than a dozen articles in medical journals from 1948 to 1958, would warrant only one of the forty-five paragraphs of his obituary in 2001, overshadowed by the work that made him a celebrity.≤ His name was William H. Masters. Born into a well-to-do family in Cleveland in 1915, Masters attended elementary school in Kansas City, prep school in Lawrenceville, New Jersey, and college at Hamilton in Clinton, New York. Masters was a star in and out of the classroom: in addition to his scientific studies, he competed on the debate team and won varsity letters in football, basketball, and baseball.≥ In the fall of 1939, he entered medical school. It was there that he met George Corner, one of the leaders in the field of reproductive biology and the co-discoverer of progesterone, the second female sex hormone. Under Corner’s direction, Masters began work on the estrous cycle of female rabbits; this research sparked his interest in human sexuality, a neglected but potentially fascinating field of study. Although Corner moved on to the Carnegie From the ‘‘Neutral Gender’’ to ‘‘Feminine Forever’’ 33 Institute in Washington, he continued to act as a mentor to Masters. When Masters expressed his desire to study the physiology of sex in men and women, Corner gave him a key piece of advice: wait until you are at least forty years old with an established record of academic credentials before you undertake such controversial research.∂ Masters heeded his teacher’s suggestion and turned his attention to hormone replacement therapy. In the mid-1950s, having passed his fortieth birthday and having achieved a scholarly reputation, Masters joined forces with Virginia Johnson and embarked on the laboratory research that would result in the publication of the best-selling book Human Sexual Response in 1966, launching his second career as one of the gurus of the sexual revolution. Masters’s first career as an investigator of sex hormones and the problem of aging led him to describe ovarian failure as ‘‘the Achilles heel’’ of the female endocrine system.∑ Because he attributed the onset of osteoporosis, cardiovascular disease, and senility to the decline of estrogen production, he argued that longterm hormone replacement therapy could improve the physical condition and mental acuity of older women. This theory contradicted the prevailing wisdom among doctors in the 1950s, namely, that estrogen should be used only for the short-term relief of menopausal symptoms. In this regard, Masters’s work on hormone replacement therapy was as revolutionary as his later investigations into the science of human sexual behavior. Fromthe1930sthroughthe1950s,doctorsincorporatedestrogenproductsinto their pharmaceutical arsenals. The dominant model, as articulated by physicianauthored articles in medical journals, called for restraint in the prescription of estrogen to alleviate menopausal symptoms.∏ In reviewing the options available to doctors treating menopausal women, one Kentucky physician told his colleagues, ‘‘The sooner the estrogens can be stopped and the patient allowed to go on her own, with good health habits, food and rest, and living within her physical capacity, the better and more permanent are the results.’’π A gynecologist from North Carolina advised, ‘‘The dosage [of estrogen] should be kept at a minimum, begun early, and discontinued, even if only temporarily, as soon as possible.’’∫ Medical consensus also held that only a small proportion of women needed to be treated with estrogen at menopause.Ω In this view, most women passed through the change with little or no trouble...